Incidence of ocular manifestations in patients with graft versus host disease after allogeneic stem cell transplant in Riyadh, Saudi Arabia

AIM: To evaluate the incidence and severity of ocular graft versus host disease(o GVHD) in patients who underwent allogeneic stem cell transplant(SCT) in King Abdul-Aziz Medical City, Saudi Arabia.METHODS: This is a retrospective cohort study conducted in King Abdul Aziz Medical City on patients who underwent allogeneic hematopoietic cell transplant(allo-HCT) from 2010 to 2017. The ocular examination findings including visual acuity, meibomian gland dysfunction, corneal and conjunctival staining with severity, corneal scarring, tear film meniscus and breakup time, anterior and posterior segment examination findings, intraocular pressure, treatment given, punctual plugs used or not, and follow up response were collected.RESULTS: The five years cumulative incidence of o GVHD among post-transplant patients was 56.98%(95%CI 38.6%-71.7%). The potential risk factors assessed for developing ocular manifestation were age, gender, donor’s age, donor gender mismatch CD3 and CD34 infusion, while none of the correlates were identified as statistically significant risk factors of developing ocular manifestation. However, the incidence was statistically significantly different betweenpatients diagnosed with acute myelocytic leukemia and acute lymphocytic leukemia(P=0.038). The mean latent period to develop ocular symptoms was 20.5 mo. All patients had variable degree of dry eyes. None of the patients developed any posterior segment complication.CONCLUSION: The incidence of o GVHD is low in King Abdul-Aziz Medical City. This can be attributed to the preconditioning and immunosuppressive regime.

Ocular Graft versus Host Disease: A Review of Clinical Manifestations, Diagnostic Approaches and Treatment

Allogenic haematological stem cell transplantation (allo-SCT) from a human leukocyte antigen (HLA) matched related or unrelated donor is used as a curative therapy for a large number of malignant and non-malignant haematological diseases. The curative effect of allo-SCT is achieved by graft versus leukaemia effect while the downside of the graft versus patient activity is the graft-versus-host-disease (GVHD), a major reason for mortality and morbidity. The search of articles for this review had been accomplished using Ovid, Medline, Embase, Pubmed and was supplemented by retrieving cross references also. Electronic literature search for English language articles with full text access was performed using graft versus host disease, ocular, management, dry eyes as key words. This review has been intended to explicate the classification, pathogenesis, risk factors and management of ocular graft versus host disease.

Advantageous tactics with certain probiotics for the treatment of graft-versus-host-disease after hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation(HSCT)becomes a standard form of cellular therapy for patients with malignant diseases.HSCT is the first-choice of immunotherapy,although HSCT can be associated with many complications such as graft-versus-host disease(GVHD)which is a major cause of morbidity and mortality after allogeneic HSCT.It has been shown that certain gut microbiota could exert protective and/or regenerative immunomodulatory effects by the production of short-chain fatty acids(SCFAs)such as butyrate in the experimental models of GVHD after allogeneic HSCT.Loss of gut commensal bacteria which can produce SCFAs may worsen dysbiosis,increasing the risk of GVHD.Expression of G-protein coupled receptors such as GPR41 seems to be upre-gulated in the presence of commensal bacteria,which might be associated with the biology of regulatory T cells(Tregs).Treg cells are a suppressive subset of CD4 positive T lymphocytes implicated in the prevention of GVHD after allogeneic HSCT.Here,we discuss the current findings of the relationship between the modification of gut microbiota and the GVHD-related immunity,which suggested that tactics with certain probiotics for the beneficial symbiosis in gut-immune axis might lead to the elevation of safety in the allogeneic HSCT.

Colonoscopy in the diagnosis of intestinal graft versus host disease and cytomegalovirus enteritis following allogeneic haematopoietic stem cell transplantation

Background Gastrointestinal graft versus host disease （GI-GVHD） and cytomegalovirus （CMV） enteritis are important complications following allogeneic haematopoietic stem cell transplantation （allo-HSCT）. We explored the role of colonoscopy in the diagnosis of GI-GVHD and CMV enteritis following alIo-HSCT to identify the endoscopic manifestations of GI-GVHD and CMV enteritis was made. Methods A retrospective analysis of the colonoscopic manifestations of GI-GVHD, CMV enteritis and GI-GVHD with concurrent CMV enteritis （GconC） and their related clinical issues. Results Forty-seven patients underwent 50 colonoscopies with diagnoses of 32 GI-GVHD, 7 CMV enteritis and 11 GconC. Both GI-GVHD and CMV enteritis had colonic mucosal lesions with various manifestations under colonoscopy. Tortoise shell like changes of the mucosa （12 of 32） and deep ulcers （2 of 7） were specific endoscopic manifestations for GI-GVHD and CMV enteritis, respectively, while mucosal oedema, erythema, congestion, erosion and shallow ulcers could not be used to differentiate GI-GVHD from CMV enteritis. GconC patients were prone to have oozing bleeding of the end ileal mucosa and typhlodicliditis. Of the biopsed specimens for GI-GVHD, CMV enteritis and GconC, 64%, 70% and 44% were taken from the rectum and sigmoid colon respectively. Conclusions Following allo-HSCT, tortoise shell like changes and deep ulcers of the colonic mucosa are characteristic changes for GI-GVHD and CMV enteritis, respectively, while the other lesions are not. Most of the GI-GVHDs and CMV enteritis cases can be diagnosed by left colon examination and tissue biopsy, but total colon examination to the terminal ileum is preferred.

PLACENTAL INTRAVENOUS IMMUNOGLOBULIN (PtIVIG) FOR TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE (CGVHD)

Plasma immunoglobulin has been used widely in clinic for the prophylaxis and treatment of infections in patients after bone marrow transplantation(BMT).However,there are no hard data demonstrating that it can act against GVHD,

Graft versus host disease after liver transplantation:A case report

In documenting clinical experience in the diagnosis and treatment of graft versus host disease(GVHD),we retrospectively analyzed data of one case that has developed GVHD after liver transplantation.This patient exhibited fever,skin rash,and diarrhea on day 9 after liver transplantation.His liver function was normal.Skin biopsy showed scattered keratinocytes accompanied by satellite-like lymphocyte infiltration and basal cell liquefaction degeneration.After carefully analyzing the complications,we took the strategy of decreasing the dose of tacrolimus.Thereafter,the patient’s temperature decreased to normal,his skin rashes subsided,and his diarrhea was relieved.This case suggests that reducing the dosage of immunosuppressive agents can be an effective strategy for GVHD after liver transplantation.

Advances in the role of follicular T helper cells in graft versus host diseases

Graft versus host disease(GVHD)is a refractory complication of allogeneic hematopoietic stem cell transplantation for the treatment of malignant and non-malignant hematopoietic diseases.Inflammatory cascade responses and cellular immune reactions are the major factors underlying GVHD pathogenesis.Cells producing the cytokine,interleukin(IL)-21 are crucial players involved in injured tissues in GVHD patients.Besides T helper 17 cells,follicular T helper(Tfh)cells are a new source of IL-21 and play a vital role in GVHD pathogenesis.Tfh cell function is mostly regulated by T-follicular regulatory(Tfr)cells that are also located in the germinal center.This review highlights recent advances in the role of Tfh and Tfr cell function in GVHD pathogenesis.New insights are provided into the potential for clinical application in GVHD prevention and treatment.

Cytokines are early diagnostic biomarkers of graft-versus-host disease in liver recipients

BACKGROUND： Graft-versus-host disease （GVHD） is associated with high mortality. Early diagnosis is essential to start treatment and to improve outcomes. Because of the inflammatory nature, we hypothesis that cytokine profile of patients with GVHD may serve as diagnostic markers. The present study was to evaluate the role of cytokine profile in the diagnosis of GVHD. METHODS： An immunoassay was used to detect 29 cytokines simultaneously in the serum; the measuring sensitivity of all cytokines was pg/mL. Healthy subjects undergoing annual routine physical examinations served as negative controls; 23 patients with hepatocellular carcinoma （HCC） who had undergone liver transplantation （the LT group） comprised the test subjects. A total of 22 kidney recipients with biopsyconfirmed GVHD （the RT group） were included for comparison. HCC patients with radical surgery （the HCC group, n=22） served as positive control. The liver contents of the three cytokines, IL-2, IL-18, and IFN-γ, were detected with immunohistochemistry. Serum granzyme B and perforin were measured by flow cytometry.RESULTS： Of the 29 cytokines, the levels of IL-2 and IL-18 were increased significantly in liver recipients with GVHD compared with healthy controls （P〈0.05）. The serum levels of these three cytokines in the healthy, HCC, LT, and RT groups were IL-2： 0.90±0.02, 4.14±0.61, 5.10±0.89, and 1.48±0.09 pg/mL; IL-18： 80.61±9.35, 109.51±10.93, 230.11±12.92, and 61.98±7.88 pg/mL; IFN-γ： 24.06±3.88, 24.84±3.21, 40.37±5.88, and 15.33±4.72 pg/mL, respectively. Immunohistochemistry showed that these 3 cytokines expressions in the liver were parallel to the serum cytokine. After standard anti-GVHD treatment, the expressions of IL-2, IL-18, and IFN-y were de- creased in the liver （P〈0.05）. Serum granzyme B and perforin were significantly increased in GVHD patients （P〈0.05）. CONCLUSIONS： IL-2, IL-18 and IFN-γ were from liver and might serve as biomarkers for monitoring GVHD develop- ment and the effects of anti-GVHD treatment. Granzyme B and perforin may play a role in increasing IL-2, IL-18, and IFN-y levels in GVHD patients.

Endoscopic diagnosis of gastrointestinal graft-versus-host disease

AIM:To evaluate the diagnostic value of endoscopy in patients with gastrointestinal graft-versus-host disease (GI GVHD). METHODS:We identified 8 patients with GI GVHD following allogeneic hematopoietic stem cell trans-plantation (HSCT). GVHD was defined histologically as the presence of gland apoptosis, not explained by other inflammatory or infectious etiologies. RESULTS:The symptoms of GI GVHD included anorexia, nausea, vomiting, watery diarrhea, abdominal pain, GI bleeding, etc. Upper endoscopic appearance varied from subtle mucosal edema, hyperemia, erythema to obvious erosion. Colonoscopic examination showed diffuse edema, hyperemia, patchy erosion, scattered ulcer, sloughing and active bleeding. Histological changes in GI GVHD included apoptosis of crypt epithelial cells, dropout of crypts, and lymphocytic infiltration in epithelium and lamina propria. The involvement of stomach and rectocolon varied from diffuse to focal. CONCLUSION:Endoscopy may play a significant role in early diagnosis of GI GVHD patients following allogeneic HSCT, and histologic examination of gastrointestinal biopsies is needed to confirm the final diagnosis.

Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation

To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C57BL/6→BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor α (TNFα) and Interferon (IFNγ) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFα were lower on day +7 than on day +3. In group B, the levels of TNFα attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFα were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNγ on day +7 were higher than on day +3. In group B, the levels of IFNγ increased progressively, but the comparison of IFNγ levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNγ attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFα are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNγ in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications.

Umbilical Cord Blood-derived Mesenchymal Stem Cells Ameliorate Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation through Multiple Immunoregulations

Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.

Fulminant gastrointestinal graft-versus-host disease concomitant with cytomegalovirus infection:Case report and literature review

Here,we report a case of fulminant gastrointestinal graft-versus-host disease(GI-GVHD) with cytomegalovirus(CMV) infection in 44-year-old woman.Despite the difficulties associated with the treatment of GIGVHD and GI-CMV disease,the mucosal findings and the clinical course showed marked improvements during long-term clinical observation.The endoscopic findings were remarkable,with diffuse sloughing mucosa in the stomach and highly active inflammation and deep discrete ulcers throughout the colon.Changes in the CMV quantitative polymerase chain reaction results were correlated with the endoscopic mucosal findings and were useful for assessing the efficacy of the treatment.Although a definite diagnosis of GI-GVHD is generally made by endoscopy with biopsy,the gross appearance of this disease can vary depending on the endoscopy.In this paper,we also conduct a literature review of patients with GI-GVHD.

Nephrotic syndrome in syngeneic hematopoietic stem cell transplantation recipients: A case report

BACKGROUND Hematopoietic stem cell transplantation(HSCT)is widely used in the treatment of hematological diseases.However,complications after transplantation,such as acute and chronic graft-vs-host disease(GVHD),still seriously affect the quality of life and even threaten the lives of patients.There is evidence that glomerular diseases can manifest as GVHD.However,GVHD should not occur as a result of syngeneic HSCT.CASE SUMMARY A 20-year-old male diagnosed with T lymphoblastic lymphoma(stage IIIA,aaIPI 1)in September 2013 was treated with six cycles of hyper-CVAD and achieved complete remission.He underwent syngeneic HSCT in June 2014,and had no kidney disease history before the transplant.However,nephrotic syndrome occurred 24 mo later in the patient after syngeneic HSCT.Renal biopsy was performed,which led to a diagnosis of atypical membranous nephropathy.After treatment with glucocorticoids combined with cyclophosphamide and cyclosporine,the nephrotic syndrome was completely relieved.CONCLUSION We report a case of delayed nephrotic syndrome after syngeneic HSCT.Antibodymediated autoimmune glomerular disease may be the underlying mechanism.After treatment with immunosuppressive agents,the nephrotic syndrome was completely relieved but further long-term follow-up is still needed.

Gene expression of cytokines after allogeneic peripheral stem cell transplantation and its relationship with acute graft-versus-host disease

Objective: To investigate the role of cytokines IL-2, IL-4, IL-10, IL-12, and IFN-γ in pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: Forty-two patients undergoing allo-PBSCT were included in this study. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to analyze gene expression of cytokines IL-2, IL-4, IL-10, IL-12, and IFN-γ. Results: All patients achieved engraftment, 18 patients developed grade ⅠGVHD, 6 patients developed grade Ⅱ-Ⅳ GVHD. The gene expression of IL-2, IL-12, and IFN-γ increased, the gene expression of IL-4 and IL-10 decreased. Conclusion: Cytokines IL-2, IL-12, and IFN-γ lead to a positive regulation of the development in human aGVHD, and IL-4 and IL-10 play negative regulatory roles.

Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease

The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses;however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., nonresponsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.

OMISSION OF DAY +11 METHOTREXATE DOES NOT APPEAR TO INFLUENCE INCIDENCE AND SEVERITY OF GRAFT-VERSUS- HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objective: To explore the influence of omission of the day +11 dose of methotrexate (MIX) on the incidence and severity of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: From April 1997 to October 2002, 80 leukemia patients (46 men and 34 women aged from 12 to 56 years with a median age of 35) underwent allo-HSCT at our BMT unit. Among them, 58 patients received grafts from HLA-identical siblings, 8 from HLA one major antigen mismatched siblings and 14 from HLA-matched unrelated donors. All patients received a modified cyclosporine and short-course MTX regimen for GVHD prophylaxis, which included MTX 15 mg on day +1, and 10 mg on days +3 and +6 (MTX day +11 dose omitted) and cyclosporine given daily. Results: The overall incidence of grade I~IV acute GVHD was 57.5% (46/80 patients), with grade II~IV acute GVHD in 28 patients (35%) and grade III~IV acute GVHD in 7 patients (8.8%). Among 58 patients receiving grafts from HLA-identical siblings, 24 patients developed grade I~IV acute GVHD (41.4%), with grade II~IV acute GVHD in 13 patients (22.4%) and grade III~IV acute GVHD in 4 patients (6.9%). 2l out of 22 patients receiving grafts from HLA one major antigen mismatched siblings and HLA-matched unrelated donors developed grade I~IV acute GVHD (95.5%), with grade II~IV acute GVHD in 14 patients (63.6%) and grade III~IV acute GVHD in 3 patients (13.6%). Chronic GVHD occurred in 38 out of 56 evaluable patients (67.9%), with extensive form in 15 patients (26.8%) and limited form in 23 patients (41.1%). With a median follow-up of 960 days (range 180~1980 days), the probability of leukemia-free survival at 3 years was 61.3% for all patients. Conclusion: Our results suggest that the day +11 MTX can be omitted without a major deleterious effect on the incidence and severity of graft-versus-host disease after HLA-identical sibling transplantation as well as HLA one major antigen mismatched sibling and HLA-matched unrelated donor transplantation.

Expressions of Tissue Factor and Tissue Factor Pathway Inhibitor in Patients with Acute Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

This study examined the expressions of human serum tissue factor （TF） and tissue factor pathway inhibitor （TFPI） in patients with acute graft-versus-host disease （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplanta-tion and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipi-ents in the absence of aGVHD or with gradeⅠaGVHD before and after the transplantation. The lev-els of serum TF and TFPI were substantially increased in the patients with gradeⅡ aGVHD at the peak of aGVHD （P〈0.05） and they were even higher in the patients with grade Ⅲ–Ⅳ aGVHD （P〈0.01）. When the conditions became stable after treatment with immunosuppressive agents, the serum TFPI level was decreased to the baseline level （P〉0.05） and the TF level was lowered but still higher than the baseline level （P〈0.05）. It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade Ⅱ–Ⅳ aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.

Unsuccessful treatment of four patients with acute graft-vs-host disease after liver transplantation

AIM: To investigate appropriate therapeutic strategies for graft-vs-host disease (GVHD) following liver transplantation. METHODS: Four patients who developed GVHD after liver transplantation in West China Hospital were included in this study. Therapeutic strategies with augmentation or withdrawal of immunosuppressants combined with supportive therapy were investigated in these patients. In addition, a literature review of patients who developed GVHD after liver transplantation was performed. RESULTS: Although a transient response to initial treatment was detected, all four patients died of complications from GVHD: one from sepsis with multiple organ failure, one from gastrointestinal bleeding, and the other two from sepsis with gastrointestinal bleeding. Few consensuses for the treatment of GVHD after liver transplantation have been reached.CONCLUSION: New and effective treatments are re-quired for GVHD after liver transplantation to improve the prognosis of patients with this diagnosis.

Graft-verse-host disease after liver transplantation:A report of two cases and review of literature

Graft-verse-host disease (GVHD) is an uncommon fatal complication following liver transplantation (LTx). In China's Mainland, only six cases have been reported with a morbidity rate up to 1%-2%. Definitive diagnosis was achieved by molecular techniques (HLA typing or PCR-STR) in only two cases and the remaining cases were diagnosed based on typical clinical features with exclusion of other possible causes. All patients died of septic shock or multiple organ failure even after administration of increased corticosteroids and supportive therapy, and reduced immunosuppressive agents. In our center, two cases of GVHD were found among 128 (1.56%) patients. One case was diagnosed by detecting lymphocyte macrochimerism through DNA-STR. Both of them died even after aggressive treatment. In China, the incidence of GVHD is similar to that reported by foreign centers except for an extremely bad prognosis. Rapid diagnosis is crucial for a better prognosis. In China, only 37.5% of cases are diagnosed by molecular methods. We recommend detecting lymphocyte macrochimerism through DNA-STR to get a rapid diagnosis, and interleukin 2-receptor antibody (basiliximab or daclizumab) therapy seems to be a good choice for the disease.

Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease

Allogeneic hematopoietic stem cell transplantation(aHSCT)is a standard validated therapy for patients suffering from malignant and nonmalignant hematological diseases.However,aHSCT procedures are limited by potentially life-threatening complications,and one of the most serious complications is acute graft-versus-host disease(GVHD).During the last decades,DNA sequencing technologies were used to investigate relationship between composition or function of the gut microbiome and disease states.Even if it remains unclear whether these microbiome alterations are causative or secondary to the presence of the disease,they may be useful for diagnosis,prevention and therapy in aHSCT recipients.Here,we summarized the most recent findings of the association between human gut microbiome changes and acute GVHD in patients receiving aHSCT.